DInhaled Anesthetics

Inhaled anesthetics, particularly halothane, have been shown to inhibit human platelet function in vitro at clinically attainable concentrations (193-196). Secondary aggregation induced by ADP and epinephrine and collagen-induced aggregation ex vivo were found to be inhibited (197) and bleeding times were frequently prolonged (194,198) in patients anesthetized with these agents. The secondary wave of aggregation induced by weak agonists was eliminated or inhibited by halothane and isoflurane, and platelet aggre-gation induced by the TP receptor agonist, STA2, was significantly suppressed by halo-thane, isoflurane andenflurane (195,196). Hirakata, et al (196) demonstrated that halo-thane (14 mM) inhibited binding of [JH]-S-145 to human platelets. The Kd increased from 0.53 nM to 14.3 nM, but B^ did not change. However, neither enflurane (20mM) nor isoflurane (20 mM) inhibited [3H]-S-145 binding. Since these concentrations substantially exceed ¿lose achieved in vivo, the significance of these findings in regard to the mechanism by which halothane inhibits platelet aggregation and prolongs the bleeding time is uncertain. Other mechanisms, such as inhibition of TXA2 formation (195), or a rise in platelet cyclic AMP (193), may also contribute . Halothane and isoflurane may have different mechanisms of action since they were observed to have differential effects on prostenoid-induced vasoconstriction of dog coronary arteries (195).